It is increasingly recognized that everyone — authors, authors' employers (e.g., an academic institution, government department, commercial company, or other), sponsors of the work, reviewers, editors, and publishers — has competing interests of some sort. It is difficult for individual readers to assess objectively whether competing interests could have biased the presentation of, peer review of, or decision to publish a given work. Transparency of competing interests allows readers to better evaluate the possibility of such bias. Authors must declare all relevant competing interests for consideration during the review process.

Editors (professional or academic, paid or unpaid) and reviewers must declare their own competing interests and if necessary disqualify themselves from involvement in the assessment of a paper.

A competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. See below for definitions and examples of various competing interests.

Who needs to declare competing interests?

Everyone involved in authorship, funding, review, and editorial decision-making of submitted articles, or who wishes to comment on or rate published articles, must declare any and all relevant competing interests

Financial competing interests include but are not limited to:

ownership of stocks or shares;

paid employment or consultancy;

board membership;

patent applications (pending or actual), including individual applications or those belonging to the institution to which the authors are affiliated and from which the authors may benefit;

research grants (from any source, restricted or unrestricted);

travel grants and honoraria for speaking or participation at meetings;gifts.

Authors must declare all potential financial competing interests involving people or organizations that might reasonably be perceived as relevant. Similarly, reviewers and academic and professional editors, paid or unpaid, must declare any financial relationships that could reasonably be perceived as relevant and/or could influence their objective review of the paper; if a financial competing interest exists, these individuals should recuse themselves from handling the paper. Anyone wishing to comment on or rate a published paper must also disclose any relevant financial interests. As a guide, any competing interest that arose within the five years either before or after the commencement of the research described, or within five years of the article being written, or within five years of events described in the article, should be declared. However, interests outside this time-frame might also be relevant; if so, they should also be declared so that their relevance can be judged by the journal editorial team.

Non-financial

Non-financial competing interests include but are not limited to:Professional:

acting as an expert witness;

membership in a government or other advisory board;

relationship (paid or unpaid) with organizations and funding bodies including nongovernmental organizations, research institutions, or charities;

membership of lobbying or advocacy organizations;

writing or consulting for an educational company.

Personal:

personal relationships (i.e. friend, spouse, family member, current or previous mentor, adversary) with individuals involved in the submission or evaluation of a paper, such as authors, reviewers, editors, or members of the editorial board;

Authors, reviewers, editors, and anyone wishing to comment on a published paper must disclose any non-financial interests that might influence their reporting, handling, or review of the paper, or that might be negatively or positively affected by publication of the paper.

For example, authors are required to declare whether they have served or currently serve on the editorial board of the journal to which they are submitting, have acted as an expert witness in relevant legal proceedings, or have sat or currently sit on a committee for an organization that may benefit from publication of the paper.

Reviewers are required to declare whether they have held grants, co-authored papers, or worked in the same institution or organization with the authors of the study they are asked to review, or if they are in an adversarial relationship with the authors.

Similarly, editors — academic or professional, paid or unpaid — are required to recuse themselves from deliberations if they cannot evaluate a paper in an objective way because of personal relationships with the authors.

Finally, anyone who comments on or rates published papers must declare non-financial competing interests at the time of posting their comments and/or rating.

HERE IS ANOTHER (BMC Journal.well well)A competing interest exists when your interpretation of data or presentation of information may be influenced by your personal or financial relationship with other people or organizations. Authors must disclose any financial competing interests; they should also reveal any non-financial competing interests that may cause them embarrassment were they to become public after the publication of the manuscript.

Authors are required to complete a declaration of competing interests. All competing interests that are declared will be listed at the end of published articles. Where an author gives no competing interests, the listing will read 'The author(s) declare that they have no competing interests'.

When completing your declaration, please consider the following questions:

Financial competing interestsIn the past five years have you received reimbursements, fees, funding, or salary from an organization that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Is such an organization financing this manuscript (including the article-processing charge)? If so, please specify.Do you hold any stocks or shares in an organization that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? If so, please specify.

Do you hold or are you currently applying for any patents relating to the content of the manuscript? Have you received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript? If so, please specify.

Do you have any other financial competing interests? If so, please specify.

Non-financial competing interests

Are there any non-financial competing interests (political, personal, religious, ideological, academic, intellectual, commercial or any other) to declare in relation to this manuscript? If so, please specify.

If you are unsure as to whether you, or one your co-authors, has a competing interest please discuss it with the editorial office.

BOTH OF THESE JOURNALS LIST FILING A PATENT AS A CONFLICT. NOW WHO PUBLISHES PAPERS AND FORGETS TO MENTION THAT THEY HAVE FILED PATENTS... I WONDER? e.g. BMC Medical Genetics 2012, 13:70 doi:10.1186/1471-2350-13-70 and WO2012123785

Disclosure of financial conflicts of interest (COI) is intended to help reviewers assess the impact of potential bias on the validity of research results; however, there have been no empiric assessments of how reviewers understand and use disclosures in article evaluation. We investigate reviewers' perceptions of potential bias introduced by particular author disclosures, and whether reviewer characteristics are associated with a greater likelihood of perceiving bias. We recommend that the monetary amount of all financial relationships be reported with manuscript submissions, lead authors certify that they have unrestricted access to data, and reviewers disclose any financial ties to industry whether or not they are related to the manuscript under review. Further research is required to better understand reviewers' perceptions of financial relationships between authors and industry in order to develop clear and consistent guidelines for incorporating the perception of potential bias into manuscript assessments.

We recommend that the monetary amount of all financial relationships....This is all very noble but is very unlikely to happen and is wishful thinking. The Universities would be itching to get a hands on the cash...Oh they probably have already and taking most or all of it. It is a year old and no one has cited this I wonder why?. This could be a first. Would half a million from a company that goes to pay for a clinical study of which you get nothing be worse than two grand consultancy that could go in your pocket or should I say the taxman's pocket or be used to send a student to a meeting or pay for lab work to be done. So unless you say what you use the cash for then it is even more complex. Team G would not exist in its present form if we did not generate funds from what ever source.

OBJECTIVES: Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS.

METHODS: Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains. Stepwise linear regression was used to predict average cognition in the patient group.

RESULTS: Most deep GM volumes were reduced in patients, with larger effects on average in men (-11%) than in women (-6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R(2) = 0.31), while lesion volume was not a significant predictor in the model.

CONCLUSIONS: Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS.

The Grey Matter is dark blue

Cognitive impairment is a known consequence of multiple sclerosis (MS), affecting roughly 50% of all patients with MS. Information processing speed and memory are the most commonly affected domains, although deficits in executive function are also frequently reported. That cognitive impairment affects meaningful activities such as work is well known. The pathophysiologic basis for cognitive dysfunction in MS is an area of great interest because a better understanding could lead to more sensitive markers and improved therapies to slow or prevent cognitive decline. MRI offers some insight into the associations between various types of tissue damage and cognitive impairment. Early studies reported moderate correlations between cognitive performance and global measures of white matter lesion volume and atrophy,and more recent studies focusing on cortical lesions and regional gray matter atrophy have demonstrated stronger associations. This study looks at different brain areas and find that shrinkage some areas are more associated with cognitive decline especially in Men.

The multiple sclerosis (MS) patient population is highly heterogeneous in terms of disease course and treatment response. We used a transcriptional profile generated from peripheral blood mononuclear cells to define the structure of an MS patient population. Two subsets of MS subjects (MSA and MSB) were found among 141 untreated subjects. We replicated this structure in two additional groups of MS subjects treated with one of the two first-line disease-modifying treatments in MS: glatiramer acetate (GA) (n = 94) and interferon-β (IFN-β) (n = 128). One of the two subsets of subjects (MSA) was distinguished by higher expression of molecules involved in lymphocyte signaling pathways. Further, subjects in this MSA subset were more likely to have a new inflammatory event while on treatment with either GA or IFN-β (P = 0.0077). We thus report a transcriptional signature that differentiates subjects with MS into two classes with different levels of disease activity.

This study has done a transcriptome analysis of white blood cells and have grouped MSers into two profile and one has a higher expression of networks of immune proteins in white blood cells than the other. This group of people had more active disease than the other group. So blood in MSers can be different but it is not clear what this says as there are other methods of saying if disease is active or not such as MRI. The authors believe that stratifying MSers into meaningful subsets in this manner has potential for personalizing care and for enhancing our understanding of MS.

Neuroanatomically precise, genome-wide maps of transcript distributions
are critical resources to complement genomic sequence data and to
correlate functional and genetic brain architecture. Here we describe
the generation and analysis of a transcriptional atlas of the adult
human brain, comprising extensive histological analysis and
comprehensive microarray profiling of ∼900 neuroanatomically precise
subdivisions in two individuals. Transcriptional regulation varies
enormously by anatomical location, with different regions and their
constituent cell types displaying robust molecular signatures that are
highly conserved between individuals. Analysis of differential gene
expression and gene co-expression relationships demonstrates that
brain-wide variation strongly reflects the distributions of major cell
classes such as neurons, oligodendrocytes,
astrocytes and microglia. Local neighbourhood relationships between
fine anatomical subdivisions are associated with discrete neuronal
subtypes and genes involved with synaptic transmission. The neocortex
displays a relatively homogeneous transcriptional pattern, but with
distinct features associated selectively with primary sensorimotor
cortices and with enriched frontal lobe expression. Notably, the spatial
topography of the neocortex is strongly reflected in its molecular
topography-the closer two cortical regions, the more similar their
transcriptomes. This freely accessible online data resource forms a
high-resolution transcriptional baseline for neurogenetic studies of
normal and abnormal human brain function

They have sequenced ( found the genetic code) of the genome (the DNA) but to make proteins the DNA has to be transcribed into RNA (the genetic code of the protein) and then translated in Protein such that amino acid building blocks of proteins are constructed into proteins. Finding the sequences of things being made is the transriptome. When things are done in biology alot of things can be being made at once so the transcriptome of one cell or one area will be different to another area. The transcriptome tells use what cells are are making (read more on this). This study maps the transcriptome of the human brain, clearly what is and will happen further is the transcriptome of the brain during MS will be explored. This type of information is important to understand human brain function in health and disease.

Re big pharma wining and dining neurologists in Michelin-starred restaurants; those days are long gone and buried. The new ABPI guidelines, and the UK bribery act, prohibit such extravagance. If we do take the opportunity to eat at the best Lyon has to offer, it will at our own expense and in the company of good friends.

When doctors talk about lesions they say 'oh, it's dead brain cells' how do they know from looking at MRI if the spots are dead or indeed re-myelinated cells? Both look white, don't they? How can somebody know without an autopsy know how much of the brain has repaired itself? Thanks.

The post-mortem MRI studies have taught us that if a lesion that is white on a T2-MRI and black or gray on a T1-MRI then it is associated with loss of axons and nerve cells. There is on caveat in that new lesions can repair themselves, i.e go from being black, to gray and then disappear. So we have to do serial scans to make sure the black or gray hole is long-standing or chronic. Similarly, MRI lesions with reduced MTR (magnetization transfer ratios) are more likely to me demyelinated. So there are ways to look at lesions using MRI and tell something about the pathological attributes. The MRI folk are clever, very clever, but they can't get to the cause of MS. MRI is a tool to help diagnose and monitor MS, but it needs other tools in parallel to pin down the cause of the disease.

This is a post in response to a comment made by a BLOGGER late last month.

Too early to allow comments in case the knights ride off into the sunset or more likely they get assassins' daggers in their backs that stops their quest and Too much attention make wake the sleeping giant

I have been reading about EBV in the aetiology MS with interest. There is certainly some intriguing evidence and (anecdotally) i had a confirmed diagnosis of EBV 2 years before my first ms symptoms.

I am however confused about how much significance the negative predictive value adds to the argument. If there is such a universal exposure to EBV in the general population (95%), then surely we would be expect to find very few MSers (if any in a sample population) to be seronegative for EBV ... as is the case.

There are less (or no if causal) that are virus negative than is found in the general population

However if you have EBV as most of the population does it does not mean you will get MS, but if it is causal then you need to have EBV to trigger the MS in someone who has gene variants that make you susceptible to getting MS in some one you has the environmental factors, e.g. smokers, vitamin D levels. Without the trigger the gun never fires.

Re: "There seems to be a group of patients that have a relatively benign RRMS course (maybe 1 or 2 relapses only) but then still go on to develop SPMS. Why do you think this is? Is it because they are still experiencing sub-clinical attacks and therefore accumulation of disability or do you think there is something different going on?"

This is what will be answered with the alemtuzumab trials. If the MSers who have been treated early with this drug turn out to have benign MS and don't develop SPMS after 2--30 years then the former is correct. If they comeback with SPMS then the latter is correct. The problem we face is can we afford to wait to find out the answer to this question? VV is clearly prepared to wait as he is convinced that relapse and MRI activity make no difference. I am not sure his correct, which is why I am a strong advocate of early aggressive treatment.

Foetal neural stem/precursor cells (NPCs) possess powerful
immunomodulatory properties which enable them to protect the brain from
immune-mediated injury. A major issue in developing neural
stem/precursor cell (NPC) therapy for chronic neuroinflammatory
disorders such as multiple sclerosis
is whether cells maintain their immune-regulatory properties for
prolonged periods of time. Therefore, we studied time-associated changes
in NPC immunomodulatory properties. We examined whether
intracerebrally-transplanted NPCs are able to inhibit early versus
delayed induction of autoimmune brain inflammation and whether
allogeneic NPC grafts continuously inhibit host rejection responses. In
two experimental designs, intraventricular foetal NPC grafts attenuated
clinically and pathologically brain inflammation during early EAE
relapse but failed to inhibit the disease relapse if induced at a
delayed time point. In correlation, long-term cultured neural precursors
lost their capacity to inhibit immune cell proliferation in vitro. Loss
of NPC immune functions was associated with transition into a quiescent
undifferentiated state. Also, allogeneic foetal NPC grafts elicited a
strong immune reaction of T cell and microglial infiltration and were
rejected from the host brain. We conclude that long-term functional
changes in transplanted neural precursor cells lead to loss of their
therapeutic immune-regulatory properties, and render allogeneic grafts
vulnerable to immunologic rejection. Thus, the immunomodulatory effects
of neural precursor cell transplantation are limited in time

This study looked at the effect of neural stem cells (stem cells that can make nerve and glial cells) to immunomodulate. They could do this when applied early in experimental disease but once disease was established they did nothing as immunomodulators. However, you do not treat MSers before they get MS. Then it says to me that neural stem cells do not immunomodulate and so much of the studies published previously is simply hype. The lab doing this study was one of those leading way to show the immunomodulation by stem cells story and this work suggests that their view will be modified about benefit. However, I think that we should not be expecting them to having dramatic or in fact any immunomodulatory effect in MS. The question is can they become myelin-repair cells? I have viewed much of the so called immunomodulation studies using stem cells with a sceptical eye and this tends to confirm this view.

Even our own work has not shown nuch immunomodulatory actions of these cells. When it does occur it is usually marginal to what can be achieved with card-carrying immunomodulatory drugs. However we shall see. There are studies with other types stem cells that have also been reported to be immunomodulatory, which are in trial in MS as we speak so we will see what happens.

"Are yiou surprised with these results? I am not. They do indicate, however, that we have a lot of work to do to get this concept accepted by the wider clinical community and more importantly into clinical practice. Let's hope the community is ready for the concept. It is very important for MSers; at least those with RRMS."

OBJECTIVE: To optimize and validate a scoring system able to discriminate responses to interferon treatment in RRMSers.METHODS: The analysis included two large, independent datasets of RRMSers who were treated with interferons that included 4-year follow-up data. The first dataset ("training set") comprised of 373 RRMSers from a randomized clinical trial of subcutaneous interferon beta-1a. The second ("validation set") included an observational cohort of 222 RRMSers treated with different interferons. The new scoring system, a modified version of that previously proposed by Rio et al., was first tested on the training set, then validated using the validation set. The association between disability progression and risk group, as defined by the score, was evaluated by Kaplan Meier survival curves and Cox regression, and quantified by hazard ratios (HRs).

RESULTS: The score (0-3) was based on the number of new T2 lesions (>5) and clinical relapses (0,1 or 2) during the first year of therapy. The risk of disability progression increased with higher scores. In the validation set, MSers with score of 0 showed a 3-year progression probability of 24%, while those with a score of 1 increased to 33% (HR = 1.56; p = 0.13), and those with score greater than or equal to 2 increased to 65% (HR = 4.60; p < 0.001).

CONCLUSIONS: The investigators report development of a simple, quantitative and complementary tool for predicting responses in interferon-treated MSers that could help clinicians make treatment decisions.

"Is this something you want? It is related to the recent discussions on disease-activity free status in trying to predict who responds to treatment or not! This is a discussion that should be happening. You should ask your neurologists to set a target and aim for that; i.e. treat-to-target or TOT. This is a concept the rheumatologists use that we should adopt. TOT was discussed at the Cleveland meeting and there was a general consensus that we should adopt the concept in MS."

Current methods for studying central nervous system myelination
necessitate permissive axonal substrates conducive to myelin wrapping by
oligodendrocytes. We have developed a neuron-free culture system in
which electron-spun nanofibers of varying sizes substitute for axons as a
substrate for oligodendrocyte
myelination, thereby allowing manipulation of the biophysical elements
of axonal-oligodendroglial interactions. To investigate axonal
regulation of myelination, this system effectively uncouples the role of
molecular (inductive) cues from that of biophysical properties of the
axon. We use this method to uncover the causation and sufficiency of
fiber diameter in the initiation of concentric wrapping by rat
oligodendrocytes. We also show that oligodendrocyte
precursor cells display sensitivity to the biophysical properties of
fibre diameter and initiate membrane ensheathment before
differentiation. The use of nanofibre scaffolds will enable screening
for potential therapeutic agents that promote oligodendrocyte differentiation and myelination and will also provide valuable insight into the processes involved in remyelination.

Making myelinating cultures is technically challenging because to have to first make nerves and then get oligodendrocytes to myelinate them. Nerves are cells that do not like to grow and so you end up using feotal cutlures to produce them or use stem cells to grow them. This study shows that you can use fibres to replace nerves and this then allows you to get an assay going to test drugs on ways to test myelination.

Friday, 28 September 2012

Epub: Sosnoff et al. Falls and physical activity in persons with multiple sclerosis. Mult Scler Int. 2012;2012:315620.Objectives: To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in MSers. Design: A community-based sample of 75 ambulatory MSers volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results: Overall, 37 MSers (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Msers who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P < .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P > .05).

Conclusions: Collectively, the findings suggest that fall history may have little impact on current physical activity levels in MSers.

"These result complement an audit we have just finished. In our audit the best predictor of falls was the need for an assistive walking device - i.e. foot splint, stick or walker - which is clearly associated with level of disability. Why is this topic important? Because MSers also have poor bone health and are signficantly increased risk of having fractures. Therefore it is important to prevent fractures; this can be done by treating thin bones and trying to prevent falls. The former is easier than the latter to do."

I would appreciate it if you could complete this short survey to see if your MS team are taking this issue seriously:

BACKGROUND: Quantitative posturography has been reported as a reliable tool to measure balance in people with multiple sclerosis (MS). However, data on its diagnostic accuracy in predicting the occurrence of falls are ...

Conclusions: Factors associated with falls in MS'ers are similar to those in other populations with neurological diseases. Despite the high incidence of falls, fewer than 50% of MS'ers receive information about prevention of ...

Background: Falls among persons with multiple sclerosis (MS) are a serious health concern and the percentage of people restricting activity due to concerns about falls is not known. Mobility function and accumulated ...

If you are having falls you need to be assessed by a physiotherapist to see if anything can be done to reduce the number and severity of your falls. Your other medications need to be reviewed; some of them may exacerbate ...

PURPOSE: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system mediated by T cells. B7-H3 plays a diverse role in regulating T cell responses. However, its expression and clinical significance in MS are not well known. This study analyzed the expression of membrane B7-H3 (mB7-H3) and levels of soluble B7-H3 (sB7-H3) in MS patients to determine its clinical significance.

METHODS: Peripheral blood (PB) or cerebrospinal fluid (CSF) samples from healthy controls, other noninflammatory neurological disorders, viral encephalitis, and MS patients were collected. Expression of mB7-H3 on immune cells was detected by flow cytometry. Levels of sB7-H3 in serum or CSF samples were measured by ELISA.

CONCLUSIONS: We demonstrated enhanced mB7-H3 expression and reduced sB7-H3 levels in MS patients which correlated with the clinical characteristics of MS patients. These results suggest that B7-H3 may be a promising biomarker and associated with the pathogenesis of MS.

B7-H3 (CD276) is a molecule with co-stimulatory function. This means that it is not part of the direct contact between a T cell and its target which involves interaction of the T cell receptor and the target presented by a macrophage (the activation-the stimulatory step), which is required to stimulate the T cell, but an addition interaction (co-stimulation) between the T cell and the macrophage that is required to make the activations step cause multiplication of the T cell. Without it they are switched off. The firs of these co-stimulatory molecules was B7-1 (CD80) and B7-2 (CD86) which interacts with CD28 and CD152. The B7-H3 is anchored into the cell membrane but it can also be cleaved and shed into the fluid outside cells and get into the blood and this is called soluble B7-H3. This can inhibit some immune functions and so it is consistent with the observation that with lower sB7-H3 there was more disease activity such that it was lower in Msers than health controls and within MSers it was lower during attacks than in remission. Is this cause or consequnce?

Is this going to be a biomarker, if is the results show significance of only p<0.05 then this is not very likely as there will be too much overlap between groups.

This reminds of a story, we wanted some fresh MSer CSF and also some healthy controls, so whilst we were asking MSers to do this we thought that we should be willing to do this also so Prof G, MouseDoctor II and Myself all volunteered to have this done. However it was not considered ethical, because of doing an unnecessary procedure with risks if it went wrong and so we never got the samples. This is another example what is OK in one country or with one committee, may not be OK in another.

Oligodendroglia support axon survival and function through mechanisms
independent of myelination, and their dysfunction leads to axon
degeneration in several diseases. The cause of this degeneration has not
been determined, but lack of energy metabolites such as glucose or
lactate has been proposed. Lactate is transported exclusively by
monocarboxylate transporters, and changes to these transporters alter
lactate production and use. Here we show that the most abundant lactate
transporter in the central nervous system, monocarboxylate transporter 1
(MCT1, also known as SLC16A1), is highly enriched within
oligodendroglia and that disruption of this transporter produces axon
damage and neuron loss in animal and cell culture models. In addition,
this same transporter is reduced in patients with, and in mouse models
of, amyotrophic lateral sclerosis, suggesting a role for
oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in
axon function and neuron survival has been elusive; this study defines a
new fundamental mechanism by which oligodendroglia support neurons and
axons.

Blood glucose (orange) can be taken up by neuronal brain cells such as oligodendrocytes and astrocyte. Inside the cell glucose is broken down to lactate (blue), which can then be transferred to nerves and used to generate energy (Yellow=Adenosine Tri Phosphate). This occurs via a transporter protein called MCT1 found in myelin. Lactate can also be produced by astrocytes and transferred to nerves through small pores in the myelin.

It has been throught that getting myelin back on demyelinated nerves is the way to help nerves survive and so slow progression. This study shows that it is not just myelin but the oligodendrocyte also give the cells energy factors which help nerves survive. One way we believe that nerves have problems is through influences on energy supply. This will determine whether nerves can survive. We know that glucose is used as an energy supply and that lactic acid builds up when we excerise. When the rate of demand for energy is high, glucose is broken down and oxidized to pyruvate,
and lactate is produced from the pyruvate faster than the tissues can
remove it, so lactate concentration begins to rise. The production of
lactate is a beneficial process because it regenerates NAD+
which is used up in the creation of pyruvate from glucose, and this
ensures that energy production is maintained and function can continue. Lactate can be transported into cells by transporters and this study found that if lactate transport is disrupted in oligodendrocytes then they cannot provide lactate to nerves which helps support life in the nerves.

This adds further weight to the idea of restoring energy metabolism to nerves is a good thing and you can really feed this into the ideas we have already made about progression in MS.

The 4th Research Day will be held in Central London on Saturday 2nd of February 2013

More to Follow

UCLPartnersis one of five accredited academic health science systems in the UK. Its purpose is to translate cutting edge research and innovation into measurable health gain for patients and populations-in London, across the UK and globally

As you know the BLOG is an Educational Tool and just so you know Prof G has been learning HTML. You can see his recent handywork resulting in lots of embedded stuff like putting surveys into the web pages.

Personally, if only I could learn pitched harmonics then maybe I could be like Zak Wylde :-)

PURPOSE:
To identify baseline predictors of the response to natalizumab in
patients with relapsing-remitting multiple sclerosis (RRMS).

METHODS:
We prospectively collected clinical and magnetic resonance imaging
(MRI) data of RRMS patients treated with natalizumab and followed-up for
24months. They were categorized according to different outcomes of
response to natalizumab: (i) "full" responders, i.e. those having no
relapses, no sustained disability worsening on Expanded Disability
Status Scale (EDSS), and no MRI activity; (ii) "partial" responders,
i.e. those having MRI activity, but not relapses and/or EDSS worsening;
and (iii) "poor" responder, i.e. those experiencing relapses and/or EDSS
worsening.

RESULTS:
We analysed data of 210 RR-MS patients (147F, 63M); at the end of the
24-month study period, 120 (57.1%), 36 (17.1%), and 54 (25.8%) patients
were defined as "full", "partial" or "poor" responders, respectively.
Thirty-two (89%) patients classified as "partial" responders experienced
MRI activity at the 6-month scan; the majority of them had >2
contrast-enhancing lesions at baseline MRI scan or >2 relapses in the
year prior to starting therapy. A "full" response to natalizumab was
found more likely in patients with ≤2 relapses in the year prior to
treatment start (OR=3.68; p=0.002), and in those with an EDSS score ≤2.5
at baseline (OR=3.60; p<0.001). Accordingly, patients with >2
relapses in the year prior to treatment start, or those with an EDSS
score ≥3.0 at baseline were more likely to be classified as "poor
responders". These figures were replicated even after excluding 20
patients who developed anti-natalizumab antibodies.CONCLUSION:
Our results suggest that natalizumab may lead to a complete remission
of MS if started in patients with less aggressive disease (i.e. few
relapses and mild disability), thus suggesting its possible role as
first switching option, or even first-line therapy, at least in
JCV-negative patients. We also support the recommendation against an
immediate discontinuation of despite the occurrence of MRI activity in
the first few months of treatment, since the freedom from clinical
disease activity could be still achieved.

Whilst posting the study on employment it is perhaps relevant that we mention this new study too. This looked at people who take Tysabri and see how well people do on this. Notably they looked to see if disease activity was squashed or whether there was some grumbling disease still going on. As can be seen this is not a cure as most people still had some disease activty, but there were some people who did very well and these were people with early and mild disease, This is further evidence for striking early with effective DMT.

PML Risk Infographic

Holistic Management of MS ver. 7.0

Search this Blog

Follow by Email

Subscribe To

Translate

Followers

Disclaimer

General Disclaimer: Please note that the opinions expressed here are those of the individual bloggers and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry, Queen Mary University of London or Barts Health NHS Trust.

Survey Disclaimer: No personal identifiers will be collected as part of these surveys. By completing these surveys you are consenting to the data you provide being analysed by Professors Giovannoni and Baker and their collaborators. Results of these surveys will be presented on this blog and may be submitted for publication.